: Ascending neurotransmitter systems from the brainstem and basal forebrain regulate activities in cortical networks through direct actions on GABAergic inhibitory interneurons. Data suggest that neurotransmitters such as acetylcholine (ACh) and serotonin (5-HT) can selectively activate particular subgroups of inhibitory interneurons through different classes of postsynaptic receptors and thus modify the flow of information in cortical circuits. These experiments will examine effects of ACh and 5-HT on low threshold spike (LTS) and fast spiking aboutS) GABAergic interneurons in layer V of rat visual cortex. about Patch-clamp techniques will be used to obtain whole cell recordings to evaluate the subtypes of cholinergic and serotonergic receptors on different subclasses of interneurons and the nature of the postsynaptic responses. In paired recordings, unitary inhibitory postsynaptic currents will be evoked on pyramidal neurons and presynaptic effects of cholinergic and serotonergic agonists will be assessed. Intracellular labeling with biocytin combined with immunocytochemistry for calcium binding proteins and neuropeptides will be used along with electrophysiological behavior to classify interneurons to further test the hypothesis that subgroups of interneurons are selectively modulated by ACh and 5-HT. Given the importance of the GABAergic inhibitory network in information processing and pathophysiologic processes such as epileptogenesis, and the observation that these ascending neurotransmitter systems may be altered anatomically following cortical lesions, information regarding action of modulators like ACh and serotonin is critical to our understanding of normal and disordered cortical function.